WOEST 3: What is the Optimal Antithrombotic Strategy in Patients Presenting With Acute Coronary Syndrome Having Atrial Fibrillation With Indication for Anticoagulants?
Study Details
Study Description
Brief Summary
The optimal antithrombotic management in patients with coronary artery disease (CAD) and concomitant atrial fibrillation (AF) is unknown. Patients with AF are treated with oral anticoagulation (OAC) to prevent ischemic stroke and systemic embolism and patients with acute coronary syndrome (ACS) or those who undergo percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), i.e. aspirin plus P2Y12 inhibitor (clopidogrel), to prevent stent thrombosis (ST) and myocardial infarction (MI). Patients with AF undergoing PCI were traditionally treated with triple antithrombotic therapy (TAT, i.e. oral anticoagulation (OAC) plus aspirin and P2Y12 inhibitor) to prevent ischemic complications. However, TAT doubles or even triples the risk of major bleeding complications. More recently, several clinical studies demonstrated that omitting aspirin, a strategy known as dual antithrombotic therapy (DAT) is safer compared to TAT with comparable efficacy.
However, pooled evidence from recent meta-analyses suggests that patients treated with DAT are at increased risk of myocardial infarction (MI), stent thrombosis (ST) and even cardiovascular (CV) death. Insights from the AUGUSTUS trial showed that aspirin added to OAC and clopidogrel for 30 days, but not thereafter, resulted in fewer severe ischemic events. This finding emphasizes the relevance of early aspirin administration on ischemic benefit, also reflected in the current ESC guideline. However, because we consider the bleeding risk of TAT unacceptably high, we propose to use a short course of DAPT (drop the OAC for 1 month). There is evidence from the BRIDGE study that a short period of omitting OAC is safe in patients with AF. In this study, these patients are treated with DAPT that also prevents stroke, albeit not as effective as OAC. Thus, by omitting OAC in the first month, we make room for aspirin use for optimal prevention of myocardial infarction or stent thrombosis in the first month after ACS or PCI.
The WOEST 3 trial is a multicentre, open-label, randomised controlled trial to investigate the safety and efficacy of one month DAPT compared to standard therapy consisting of OAC and P2Y12 inhibitor combined with aspirin up to 30 days. We hypothesise that the use of short course DAPT is superior in bleeding and, secondary, non-inferior in preventing ischemic events. The primary endpoint is clinically relevant bleeding (according to the International Society of Thrombosis and Haemostasis definition) after one month. Secondary endpoints include a composite of CV death, MI, ischemic stroke, ST, and systemic embolism after one month, and one year follow-up.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: First month DAPT
|
Drug: First month DAPT
One month of aspirin + P2Y12 inhibitor followed by 11 months of oral anticoagulants + P2Y12 inhibitor
|
| Active Comparator: First month standard therapy
|
Drug: First month standard therapy
One month of oral anticoagulant + P2Y12 inhibitor + limited duration of aspirin as per international guidelines (during hospitalization or 7 days; up to 30 days for high thrombotic risk patients); followed by 11 months of oral anticoagulants + P2Y12 inhibitor
|
Outcome Measures
Primary Outcome Measures
- Bleeding complications [30 days]
Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis
Secondary Outcome Measures
- Thromboembolic complications [30 days]
Composite thrombotic end point of all-cause death, myocardial infarction, stent thrombosis, ischemic stroke, and systemic embolism
- Thromboembolic complications [1 year]
Composite thrombotic end point of all-cause death, myocardial infarction, stent thrombosis, ischemic stroke, and systemic embolism
- Bleeding complications [1 year]
Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis
- Ischemic stroke [30 days]
Ischemic stroke
- Net clinical benefit [30 days]
Cardiovascular mortality, myocardial infarction, stent thrombosis, stroke, systemic embolism and clinically relevant bleeding as defined by the international society of thrombosis and haemostasis criteria
- Net clinical benefit [1 year]
Cardiovascular mortality, myocardial infarction, stent thrombosis, stroke, systemic embolism and clinically relevant bleeding as defined by the international society of thrombosis and haemostasis criteria
Other Outcome Measures
- Quality of life assessed by EuroQol-5D-5L questionnaire [30 days, 12 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients ≥ 18 years
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Presenting with ACS with elevated cardiac markers (CK/CK-MB, troponin) or undergoing PCI
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Documented or newly diagnosed non-valvular AF (<72 hours after ACS) treated with OAC or intention to treat >1 year
Exclusion Criteria:
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History of ischemic stroke
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Mechanical prosthetic heart valve
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<3 months after venous thromboembolism
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CHA2DS2-VASc >5
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Intracardiac thrombus
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Rheumatic valve disease
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Moderate/severe mitral valve stenosis
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Conditions other than atrial fibrillation that require anticoagulation for which direct oral anticoagulants will not be sufficient (e.g. prosthetic mechanical heart valve, antiphospholipid syndrome)
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History of known coagulopathy
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Estimated Glomerular Filtration Rate < 15 mL/min/1.73m^2
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- St. Antonius Hospital
Investigators
- Principal Investigator: Jurriën M ten Berg, MD, PhD, St. Antonius Ziekenhuis Nieuwegein, The Netherlands
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NL71116.100.20